title: PET measurement of receptor occupancy as a tool to guide dose selection in neuropharmacology: are we asking the right questions?
abstract: Receptor occupancy studies are becoming commonplace for verifying drug mechanism of action and selecting early development candidates. Positron emission tomography (PET) has been applied to pharmacodynamic (PD) studies in several therapeutic areas including neurology, cardiology, and oncology. Prospective use of PET to define dosing requirements has been proposed particularly for central nervous system (CNS)-targeted drugs; however, correlations with clinical outcomes have been mostly anecdotal and not causally established.
authors.affiliation: From the *Laboratory for Applied PK/PD, Division of Clinical Pharmacology and Therapeutics, Divisions of †Neurology, and ‡Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Barrett
authors.forename: Jennifer
authors.initials: J
authors.lastname: McGuire
authors.forename: Heather
authors.initials: H
authors.lastname: Vezina
authors.forename: Serguei
authors.initials: S
authors.lastname: Spitsin
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D009480:Neuropharmacology / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D002491:Central Nervous System Agents